Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that erythromycin lactobionate (EMLB) acts as a motilin agonist and is able to accelerate gastric emptying in diabetic gastroparesis. Using the rabbit as a model, we have studied the changes in motilin receptor density induced by EMLB (a motilin agonist) and octreotide (a somatostatin analogue and an inhibitor of motilin secretion). Binding studies were performed with antral smooth muscle tissue homogenates using iodinated nor-leucine13-porcine-motilin, and binding parameters were obtained from computerized fits to displacement curves. The contractile capacity towards motilin (10(-7) M) and EMLB (10(-5) M) was measured isotonically on duodenal segments and the response was expressed relative to the maximum obtained with ACh (10(-4) M). The first hours after the last i.v. administrations of EMLB (50 mg/day given on 3 consecutive days), motilin binding was completely abolished to 0.02 +/- 0.006 fmol/mg protein, compared to the control group (0.64 +/- 0.12 fmol/mg protein). The effect was dose-related: total doses of 17.5 mg, 87.5 mg, 175 mg EMLB reduced motilin binding and contractility towards motilin and EMLB to respectively 95 +/- 10, 82 +/- 5%; 36 +/- 9, 38 +/- 9%; 3 +/- 1, 24 +/- 2% of the control values. The effect was also long lasting: binding was still reduced to 60% of the control value 48 h after the highest dose. In contrast, octreotide induced a marked but short lasting upregulation. After 3 daily s.c. injections of 5 micrograms, Bmax rose to 13.6 +/- 1.9 fmol/mg protein (P less than 0.05). It was already obtained 1 h after 3 x 2.5 micrograms/24 h. The changes in receptor-density were not related to changes in affinity. We conclude that motilin receptors can be regulated by EMLB and octreotide presumably because one compound mimicks hypermotilinemia, the other one induces hypomotilinemia.
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PMID:Effect of erythromycin and of octreotide on motilin receptor density in the rabbit. 203 24

Eight patients with postprandial hypotension and orthostatic hypotension were treated with the somatostatin analogue SMS-201-995. Low doses of this drug (0.2-0.4 microgram/kg) raised the blood pressure after breakfast in all six patients with postprandial hypotension. 60 min after breakfast the mean sitting blood pressure was 35 +/- 10 (SEM) mm Hg higher after administration of SMS-201-995 0.4 microgram/kg than after placebo (p less than 0.001). Larger doses (up to 1.6 micrograms/kg) raised upright blood pressure during the postprandial period in five of seven patients. Before therapy three patients were unable to stand after eating; after an injection of SMS-201-995 0.8 microgram/kg at the beginning of breakfast they were able to walk for 35-100 min. The duration of therapeutic effect of each injection was 3-6 h. Treatment was followed by abdominal cramps and nausea in two patients with gastroparesis diabeticorum. SMS-201-995 holds promise as a treatment for postprandial hypotension and orthostatic hypotension.
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PMID:Treatment of autonomic neuropathy with a somatostatin analogue SMS-201-995. 287 21

The somatostatin analogue, octreotide, restores normal pressure profiles in disorders of upper gut motility. This study aimed to evaluate the acute effects of octreotide in five healthy subjects and in 50 consecutive patients with functional (n = 22) or organic (n = 28) dysmotility. Antroduodenojejunal manometry was performed during three hours' fasting, for two hours after a standard meal, and 30 minutes after subcutaneous injection of 50 micrograms octreotide. Antral motility, before and after octreotide, and characteristics of spontaneous migrating motor complexes and octreotide induced activity fronts were compared. Octreotide inhibited antral motility and induced a small intestinal activity front followed by motor quiescence in all healthy subjects and patients. The duration and propagation velocity of activity fronts were greater than those of spontaneous migrating motor complexes. Thirty per cent of activity fronts began simultaneously at different levels of small bowel, and in 20%, a second, normally propagated activity front developed within 30 minutes of octreotide injection. Octreotide induces rapidly propagated, long activity fronts, even in patients with neuropathology, and this may initially facilitate the intestinal propulsion of chyme. Propulsion may not occur, however, if octreotide induces simultaneous activity fronts or if the activity front is followed by prolonged quiescence. Inhibition of antral motility suggests that octreotide may not be effective in gastroparesis.
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PMID:Effect of octreotide on gastrointestinal pressure profiles in health and in functional and organic gastrointestinal disorders. 792 7

In 30 patients a reconstructive technique was used after pylorus-preserving pancreaticoduodenectomy in which the anastomoses were constructed in the sequence: duodenojejunal, hepaticojejunal (8-10 cm distal) and finally duct-to-mucosa pancreaticojejunal to a separate Roux loop. Indications for surgery included periampullary tumours, (n = 13), carcinoma of the head of the pancreas (n = 10) and chronic pancreatitis (n = 4). No patient required prolonged (> 7 days) nasogastric intubation for primary gastroparesis in the early postoperative period. Postoperative morbidity (17% overall) delayed recovery and return of gastrointestinal function in one patient with a minor biliary leak (closed with 5 days' somatostatin treatment). Other morbidity included gastrointestinal haemorrhage (n = 1), wound infection (n = 2) and respiratory infection (n = 2). There were no pancreatic leaks. One patient died from a subhepatic abscess (mortality 3%). Retrospective investigations, at 3-18 months postoperatively, included endoscopy (normal in 20 patients, none taking anti-ulcer therapy), gastric emptying studies in the first 10 patients (no delay) and bentiromide test in 12 patients considered to have normal pancreatic remnants (all patients > 24% PABA excretion index). All patients who underwent resection for tumour returned to their preoperative weight.
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PMID:A novel reconstructive technique for pylorus-preserving pancreaticoduodenectomy: avoidance of early postoperative gastric stasis. 809 56

In summary, although gastric emptying disorders are relatively uncommon, they are potentially devastating conditions resulting from pathophysiologic motor disturbances. Rapid gastric emptying of liquids is the hallmark of the dumping syndrome and occurs after operations, including vagotomy. Vagal denervation abolishes receptive relaxation and accommodation in the proximal stomach (the storage site for ingested liquids) resulting in increased intragastric pressure which forces liquids through an ablated or bypassed pylorus. Dumping symptoms may occur in up to 50% of postgastrectomy patients, but most patients are treated satisfactorily by dietary manipulation or, in the rare incapacitated patient, by the long-acting somatostatin analogue octreotide. Reconstructive gastric surgery may rarely be indicated to slow gastric emptying and alleviate the dumping syndrome. Reoperative procedures include pyloric reconstruction after pyloroplasty, small intestinal pouches, interposed isoperistaltic and antiperistaltic jejunal segments, and a Roux-en-Y gastrojejunostomy. Interposed jejunal loops and the Roux-en-Y gastrojejunostomy provide the most satisfactory results. Delayed gastric emptying may occur in the acute postoperative period or be a late complication of gastric surgery. Loss of vagal input to the gastric antrum and resection of the antrum with vagotomy may produce an atonic stomach or atonic gastric remnant, respectively, which fails to grind and propel solids into the small intestine. Scintigraphic imaging of both the liquid and solid components of the meal is a valuable diagnostic adjunct. Gastric ileus occurring in the early postoperative period generally resolves within 6 weeks of operation, and the temptation to reoperate on a nonobstructed stomach should be avoided. Pharmacologic therapy of chronic gastric stasis with the benzamide prokinetic agents (metoclopramide, cisapride, renzapride), domperidone, and the motilin agonist erythromycin, may be effective initially, but long-term results are still undefined, and postvagotomy and postgastrectomy patients have not been studied adequately. Persistent postoperative gastric atony and the Roux stasis syndrome should be managed surgically by near-total gastrectomy which should result in symptomatic improvement in two thirds of patients.
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PMID:Diagnosis and management of gastric emptying disorders. 814 Sep 75

The migrating motor complex (MMC) is a cyclic, recurring motility pattern that occurs in the stomach and small bowel during fasting; it is interrupted by feeding. The MMC is present in the gastrointestinal tract of many species, including humans. The complex can be subdivided into four phases, of which phase III is the most active, with a burst of contractions originating from the antrum or duodenum and migrating distally. Control of the MMC is complex. Phase III of the MMC with an antral origin can be induced in humans through intravenous administration of motilin, erythromycin or ghrelin, whereas administration of serotonin or somatostatin induces phase III activity with duodenal origin. The role of the vagus nerve in control of the MMC seems to be restricted to the stomach, as vagotomy abolishes the motor activity in the stomach, but leaves the periodic activity in the small bowel intact. The physiological role of the MMC is incompletely understood, but its absence has been associated with gastroparesis, intestinal pseudo-obstruction and small intestinal bacterial overgrowth. Measuring the motility of the gastrointestinal tract can be important for the diagnosis of gastrointestinal disorders. In this Review we summarize current knowledge of the MMC, especially its role in health and disease.
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PMID:The migrating motor complex: control mechanisms and its role in health and disease. 2245 Mar 6

The aim of the present study was to explore the role of orphan G protein-coupled receptor 55 (GPR55) in diabetic gastroparesis (DG). Streptozotocin (STZ) was used to mimic the DG model, and the body weight and blood glucose concentration were tested 4 weeks after STZ injection (i.p.). Electrogastrogram and phenolsulfonphthalein test were used for detecting gastric emptying. Motilin (MTL), gastrin (GAS), vasoactive intestinal peptide (VIP), and somatostatin (SS) levels in plasma were determined using radioimmunology. Real-time PCR and Western blot were applied to identify the expression of GPR55 in gastric tissue, and immunohistochemistry was used to detect the distribution. The effect of lysophosphatidylinositol (LPI), an agonist of GPR55, was observed. STZ mice showed increased blood glucose concentration, lower body weight, decreased amplitude of slow wave, and delayed gastric emptying. LPI antagonized these effects of STZ. Compared to the control group, STZ caused significant decreases of MTL and GAS levels (P < 0.01), as well as increases of SS and VIP levels (P < 0.01). The changes of these hormones induced by STZ were counteracted when using LPI. GPR55 located in mice stomach, and it was up-regulated in DG. Although LPI showed no effects on the distribution and expression of GPR55 in normal mice, it could inhibit STZ-induced GPR55 up-regulation. These results suggest GPR55 is involved in the regulation of gastric movement of DG, and may serve as a new target of DG treatment. LPI, an agonist of GPR55, can protect against STZ-induced DG, and the mechanism may involve the change of GPR55 expression and modification of gastrointestinal movement regulating hormones.
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PMID:[Role of orphan G protein-coupled receptor 55 in diabetic gastroparesis in mice]. 2496 51

Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies.
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PMID:The Role of GI Peptides in Functional Dyspepsia and Gastroparesis: A Systematic Review. 3225 3